A combination of indirect immunoprecipitation analysis, pulse chase biosynthesis and enzyme digestions indicated that Mab 9.2.27 recognizes both a released chondroitin sulfate proteoglycan (CSP; Mr 780K), its core glycoprotein (Mr 250K) and several N-linked glycoprotein precursors (Mr 210, 220, 240K) in human melanoma cells. When used in an immunotherapy model, Mab 9.2.27 injected into athymic mice bearing human melanoma tumors significantly suppressed the growth of these tumors by 70%. When conjugated to mouse effector cells, Mab 9.2.27 evoked significant and specific directed antibody-dependent cellular cytotoxicity (ADCC) in vitro against melanoma target cells that was superior to that achieved by the same amount of Mab 9.2.27 used without effector cells. More importantly, conjugates of Mab 9.2.27 IgG with mouse effector cells clearly proved most effective in almost completely (approx. 95%) suppressing growth of human melanoma tumors in athymic (nu/nu) mice. Based on some of these data, phase I clinical trials were initiated at the National Cancer Institute's Frederick Cancer Center in collaboration with R. Oldham, M.D. and colleagues. Initial results obtained with six of seven stage IV melanoma patients proved most encouraging as no detectable antibody was produced to mouse IgG and a modest decrease in tumor size and improvements in liver functions could be observed. These data suggest that Mab 9.2.27 may prove to be an additional treatment modality useful in immunotherapy and immunoprophylaxis of human malignant melanoma.